Osteoarthritis, KneeNCT06054633
L-arginine for Knee Osteoarthritis Patients
A study testing L-arginine tablet in people with Osteoarthritis, Knee, run by Xiangya Hospital of Central South University at 1 site in China.
Trial summary
This study will examine the pain-relief efficacy and safety of L-arginine in knee OA patients. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Osteoarthritis, Knee
- What is being tested?
- L-arginine tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 340 participants
- Where
- 1 siteChina
- Study dates
- 20 Mar 2024to 30 Sep 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 40 and 80 years.
- Knee OA according to the American College of Rheumatology (ACR) clinical criteria.
- Knee pain lasting 3 months or longer and a score of 7 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (standardized to range from 0-20).
- Kellgren-Lawrence (KL) grade 2 or 3.
- Willing to and able to provide written informed consent.
Who cannot join
- Any use of NSAIDs or other analgesics in the past two weeks.
- History of injections of corticosteroids in the past three months or hyaluronic acid in the past 6 months in the index knee.
- History of arthroscopy or open surgery in the index knee in the past 12 months.
- History of a knee replacement in the index knee or planning to receive such a procedure within 3 months.
- History of a severe injury in the index knee.
- Pain in the index knee caused by inflammatory, autoimmune, neoplastic diseases or other diseases.
Show all 12Show fewer
- Abnormal liver or kidney functions, as defined by alanine transaminase or aspartate aminotransferase >two times the upper limit of normal, or blood urea nitrogen or serum creatinine >two times the upper limit of normal.
- Severe respiratory diseases.
- History of coronary artery disease and heart failure.
- Uncontrolled hypertension or diabetes mellitus.
- Diagnosis of malignant tumors.
- Pregnant or contemplating pregnancy or breast-feeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xiangya Hospital
Changsha, Hunan, 410008
Guanghua Lei, Prof., 86-13808429640, lei_guanghua@csu.edu.cn
About this study
Official title: Efficacy and Safety of Oral L-Arginine for Pain Relief in Knee Osteoarthritis: a Randomized, Double-Blind, Placebo-Controlled Trial
This study will examine the pain-relief efficacy and safety of L-arginine in knee OA patients.
Read the detailed description
Pain is the dominant symptom of knee osteoarthritis (KOA). The main management goal for people with KOA is to control pain without increasing treatment-related adverse effects (AEs). However, the commonly prescribed systemic analgesics have safety concerns, such as increased risk of cardiovascular and gastrointestinal AEs. Therefore, it is urgent to develop safe and effective treatment options.
L-arginine is one of the most commonly used oral nutritional supplements that has been widely used in patients with peripheral arterial disease, cystic fibrosis, and pregnant women with high risk of pre-eclampsia. The supplement has a high safety profile. Previous case-control and cross-sectional studies have found plasma L-arginine levels were lower in patients with knee OA than controls, suggesting that arginine deficiency may increase the risk of OA. The investigators previously observed an inverse dose-response relationship between levels of serum L-arginine and the risk of incident symptomatic KOA. Additionally, the investigators demonstrated that intra-articular injection of L-arginine solution relieved pain symptoms in a surgical rat model of OA. However, there is a paucity of high-quality clinical evidence on the effect of intake of L-arginine supplement on pain relief among patients with symptomatic KOA.
The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of oral L-arginine in patients with knee OA.
- Conditions
- Osteoarthritis, Knee
- Being tested
- L-arginine tablet, Placebo tablet
- Keywords
- osteoarthritis, L-arginine, Pain
- Medical subject headings
- Osteoarthritis, Knee, Osteoarthritis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginine tabletDietary supplement
L-arginine, 2 g, three times daily, for 12 weeks
Placebo tabletDietary supplement
Identical inert placebo, three times daily, for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Oral L-arginine | Active comparator | Participants in the intervention arm will receive oral L- arginine tablets, 2 g three times daily Receives: Dietary Supplement: L-arginine tablet |
| Placebo | Placebo comparator | The control group will receive an identical inert placebo tablet, three times daily Receives: Dietary Supplement: Placebo tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
Measured: Baseline, Week 12
Secondary outcomes (14)
Change From Baseline in WOMAC pain score.
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
Measured: Baseline, Weeks 2, 4 and 8
Change From Baseline in Knee pain on a visual analogue scale (VAS).
Knee pain will be graded by a VAS from 0 to 100 mm, with 0 indicating "No pain" and 100 indicating "Worst possible pain".
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in WOMAC total score.
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of this index have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Change From Baseline in WOMAC stiffness score.
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in WOMAC function score.
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Patient global assessment of osteoarthritis (PGA-OA) score.
PGA-OA score will be assessed using a 100 mm visual analogue scale (higher is worse).
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in SF-12 questionnaire score.
The SF-12 Quality of Life questionnaire includes 8 multi-item domains (physical function, social function, role-emotional, role-physical, bodily pain, general health, mental health, and vitality). These can be combined into 2 summary measures (physical and mental component summary measures).
Measured: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Timed Up and Go Test (TUG).
TUG is a functional performance measure specifically studied in persons with OA of the hip and knee, which directly evaluates an individual's ability to transfer, ambulate, and maintain balance during transitions. The TUG assesses the time it takes participants to get up from a standard-height chair, walk 3 m, turn and return to the chair, and sit down again. The TUG has good interrater and intrarater reliability and validity for functional testing in older adults.
Measured: Baseline, Weeks 4, 8 and 12
Change From Baseline in Chair-stand Test.
The chair-stand test will use a standard chair with a 47-cm seat height. Participants start the test seated, with arms crossed over the chest, and are instructed to rise to a full stand and return to the initial seated position as many times as possible in 30 seconds. The total number of completed chair stands is averaged across two trials and used for analysis. A greater number of chair stand repetitions is interpreted as better performance.
Measured: Baseline, Weeks 4, 8 and 12
Change From Baseline in Ultrasound-assessed knee synovitis.
Both knees will be assessed with the participant supine and the knee in 30° flexion. The suprapatellar bursa will be scanned according to the Outcome Measures in Rheumatology (OMERACT) atlas. Maximal depth of effusion and synovial thickness will be measured in millimeters. Power Doppler signal observed in the synovial membrane in both longitudinal and transverse planes will be scored using a semi-quantitative grading system, from 0 to 3 (0 = absent, 1 = mild, 2 = moderate, 3 = marked or severe).
Measured: Baseline, Week 12
Rescue medicine consumption.
The consumption of rescue medication will be recorded at each visit and in the daily logs.
Measured: Weeks 2, 4, 8 and 12
Change From Baseline in Level of C-reactive protein (CRP).
The blood samples will be collected in the morning after an overnight fast at baseline and the following visits to measure the level of CRP in serum.
Measured: Baseline, Weeks 4, 8 and 12
Change From Baseline in Microbiota diversity and composition.
Stool and saliva samples will be collected at baseline and the following visits. Microbial diversity will be quantified via the Shannon diversity index (α diversity) and unweighted Unifrac distance (β diversity), and microbiota composition will be identified on different levels, including phylum, family, and genus.
Measured: Baseline, Weeks 4, 8 and 12
Incidence of adverse events and serious adverse events.
Adverse events and serious adverse events will be measured and recorded.
Measured: Weeks 2, 4, 8 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2023
- Study start20 Mar 2024
- Primary completion30 Sep 2025 (estimated)
- Study completion30 Sep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Osteoarthritis, KneeStudies of the same condition, open and under way.
- More trials run by Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 340 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xiangya Hospital of Central South University
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, School of Medicine, University of Nottingham, Memorial University of Newfoundland
- Responsible party
- Sponsor
- Investigators
- Guanghua Lei, MD, PhD, Principal investigator, Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06054633
- Sponsor's protocol ID
- 20230608
- Status last verified
- May 2025
- First submitted
- 17 Sep 2023
- Last updated
- 2 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Oral L-Arginine for Pain Relief in Knee Osteoarthritis: a Randomized, Double-Blind, Placebo-Controlled Trial
- ClinicalTrials.gov ID
- NCT06054633
- Acronym / sponsor ID
- 20230608
- Conditions
- Osteoarthritis, Knee
- Keywords
- osteoarthritis, L-arginine, Pain
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 340 participants (estimated)
- Lead sponsor
- Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, School of Medicine, University of Nottingham, Memorial University of Newfoundland
- Study start
- 20 Mar 2024 (actual)
- Primary completion
- 30 Sep 2025 (estimated)
- Study completion
- 30 Sep 2025 (estimated)
- First posted
- 26 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine the pain-relief efficacy and safety of L-arginine in knee OA patients.
Detailed description
Pain is the dominant symptom of knee osteoarthritis (KOA). The main management goal for people with KOA is to control pain without increasing treatment-related adverse effects (AEs). However, the commonly prescribed systemic analgesics have safety concerns, such as increased risk of cardiovascular and gastrointestinal AEs. Therefore, it is urgent to develop safe and effective treatment options.
L-arginine is one of the most commonly used oral nutritional supplements that has been widely used in patients with peripheral arterial disease, cystic fibrosis, and pregnant women with high risk of pre-eclampsia. The supplement has a high safety profile. Previous case-control and cross-sectional studies have found plasma L-arginine levels were lower in patients with knee OA than controls, suggesting that arginine deficiency may increase the risk of OA. The investigators previously observed an inverse dose-response relationship between levels of serum L-arginine and the risk of incident symptomatic KOA. Additionally, the investigators demonstrated that intra-articular injection of L-arginine solution relieved pain symptoms in a surgical rat model of OA. However, there is a paucity of high-quality clinical evidence on the effect of intake of L-arginine supplement on pain relief among patients with symptomatic KOA.
The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of oral L-arginine in patients with knee OA.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Oral L-arginine | Active comparator | Dietary Supplement: L-arginine tabletParticipants in the intervention arm will receive oral L- arginine tablets, 2 g three times daily |
| Placebo | Placebo comparator | Dietary Supplement: Placebo tabletThe control group will receive an identical inert placebo tablet, three times daily |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age between 40 and 80 years.
- Knee OA according to the American College of Rheumatology (ACR) clinical criteria.
- Knee pain lasting 3 months or longer and a score of 7 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (standardized to range from 0-20).
- Kellgren-Lawrence (KL) grade 2 or 3.
- Willing to and able to provide written informed consent.
Key exclusion criteria (12 listed)
- Any use of NSAIDs or other analgesics in the past two weeks.
- History of injections of corticosteroids in the past three months or hyaluronic acid in the past 6 months in the index knee.
- History of arthroscopy or open surgery in the index knee in the past 12 months.
- History of a knee replacement in the index knee or planning to receive such a procedure within 3 months.
- History of a severe injury in the index knee.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginine tabletL-arginine, 2 g, three times daily, for 12 weeks | Dietary supplement | Oral L-arginine |
| Placebo tabletIdentical inert placebo, three times daily, for 12 weeks | Dietary supplement | Placebo |
Primary outcome
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
Time frame: Baseline, Week 12
WOMAC is a self-administered, disease-specific questionnaire that assesses the severity of OA symptoms. The reliability and validity of WOMAC have been confirmed in many clinical trials. WOMAC subscales consist of pain (5 items), stiffness (2 items), and physical function (17 items). Each item is rated from 0 to 4, totaling scores of 0-20, 0-8, and 0-68 for pain, stiffness, and function subscales, respectively.
14 secondary outcomes
Change From Baseline in WOMAC pain score.
Time frame: Baseline, Weeks 2, 4 and 8
Change From Baseline in Knee pain on a visual analogue scale (VAS).
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in WOMAC total score.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Change From Baseline in WOMAC stiffness score.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in WOMAC function score.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Patient global assessment of osteoarthritis (PGA-OA) score.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in SF-12 questionnaire score.
Time frame: Baseline, Weeks 2, 4, 8 and 12
Change From Baseline in Timed Up and Go Test (TUG).
Time frame: Baseline, Weeks 4, 8 and 12
Change From Baseline in Chair-stand Test.
Time frame: Baseline, Weeks 4, 8 and 12
Change From Baseline in Ultrasound-assessed knee synovitis.
Time frame: Baseline, Week 12
Rescue medicine consumption.
Time frame: Weeks 2, 4, 8 and 12
Change From Baseline in Level of C-reactive protein (CRP).
Time frame: Baseline, Weeks 4, 8 and 12
Change From Baseline in Microbiota diversity and composition.
Time frame: Baseline, Weeks 4, 8 and 12
Incidence of adverse events and serious adverse events.
Time frame: Weeks 2, 4, 8 and 12
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jun 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Guanghua Lei, MD, PhD principal investigator
Xiangya Hospital of Central South University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-arginine tablet in people with Osteoarthritis, Knee, run by Xiangya Hospital of Central South University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yilun Wang, MD, PhD (86-18692267896, yilun_wang@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. (time frame: Baseline, Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jun 2025.